McQueen D S, Dashwood M R, Cobb V J, Bond S M, Marr C G, Spyer K M
Department of Pharmacology, University of Edinburgh Medical School, UK.
J Auton Nerv Syst. 1995 Jun 25;53(2-3):115-25. doi: 10.1016/0165-1838(94)00179-n.
The effects of ET-1 and ET-3 on ventilation and carotid chemosensory discharge have been studied in rats anaesthetised with pentotarbitone. Autoradiographic studies were also performed in vitro to investigate the binding of [125I]ET-1 to rat carotid body, nodose ganglion and brain stem. ET-1 caused a dose-related hyperventilation that was abolished by cutting both carotid sinus nerves. Recordings of chemosensory discharge from the carotid sinus nerve confirmed that ET-1 caused chemoexcitation. ET-3 had only slight effects. The hyperventilation evoked by ET-1 was antagonised by the ETA receptor antagonist FR139317, but responses to hypoxia (10% oxygen) and to cyanide were unaffected. [125I]ET-1 bound to the carotid body, the nodose ganglion and to the brain stem, particularly in the region of the nucleus tractus solitarii. ET-1 binding in the carotid body was displaceable by FR139317, which is consistent with the functional evidence for ETA receptors in the carotid body. The effects of ET-1 on ventilation, coupled with the presence of ET binding sites in areas involved in respiratory and cardiovascular regulation, is consistent with a physiological role for ET in the control of respiration, but our evidence suggests that ET is not crucial for chemotransduction in acute hypoxia.
在戊巴比妥麻醉的大鼠中研究了内皮素 -1（ET-1）和内皮素 -3（ET-3）对通气和颈动脉化学感受性放电的影响。还进行了体外放射自显影研究，以研究[125I]ET-1与大鼠颈动脉体、结状神经节和脑干的结合。ET-1引起剂量相关的通气过度，切断双侧颈动脉窦神经后这种通气过度消失。来自颈动脉窦神经的化学感受性放电记录证实ET-1引起化学兴奋。ET-3只有轻微作用。ET-1诱发的通气过度被ETA受体拮抗剂FR139317拮抗，但对低氧（10%氧气）和氰化物的反应不受影响。[125I]ET-1与颈动脉体、结状神经节和脑干结合，特别是在孤束核区域。ET-1在颈动脉体中的结合可被FR139317取代，这与颈动脉体中ETA受体的功能证据一致。ET-1对通气的影响，以及在参与呼吸和心血管调节的区域存在ET结合位点，与ET在呼吸控制中的生理作用一致，但我们的证据表明ET对急性低氧时的化学转导并不关键。
